RPGRIP1L

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Description

The RPGRIP1L (RPGRIP1 like) is a protein-coding gene located on chromosome 16.

RPGRIP1L is a human gene that encodes a protein localized to primary cilia and centrosomes in ciliated human epithelial kidney cells and retinal pigment epithelial cells. This protein colocalizes at the basal body-centrosome complex with NPHP4, NPHP6, and TUBG1. It can also interact with MyosinVa. Mutations in the RPGRIP1L gene are linked to Joubert syndrome, Meckel syndrome, and nephronophthisis, all developmental autosomal recessive disorders associated with cilium dysfunction. Copy number variation affecting the gene has been associated with schizophrenia in one study. A genetic variation within the RPGRIP1L gene (rs3213758) is linked to increased BMI. Genetic variations within the FTO gene, which are strongly associated with obesity, have also been implicated in the control of RPGRIP1L expression. Mice with decreased expression of RPGRIP1L are fatter, eat more, have diminished sensitivity to leptin (a hormone that normally reduces food intake), and display altered morphology of the brain center that regulates feeding. Similarly, cells derived from Joubert patients with RPGRIP1L mutations have decreased leptin sensitivity, and neurons important for food intake segregating for obesity-risk variations at the FTO locus have decreased RPGRIP1L expression and diminished outgrowth. These studies suggest that RPGRIP1L is important in human obesity.

RPGRIP1L negatively regulates signaling through the G-protein coupled thromboxane A2 receptor (TBXA2R). It may be involved in mechanisms like programmed cell death, craniofacial development, patterning of the limbs, and formation of the left-right axis. RPGRIP1L is involved in the organization of apical junctions, potentially through a NPHP1-4-8 module. It does not appear to be strictly required for ciliogenesis. RPGRIP1L is involved in establishing planar cell polarity, such as in cochlear sensory epithelium, possibly by stabilizing disheveled proteins. It also contributes to the regulation of proteasomal activity at the primary cilium, likely through its association with PSDM2.

RPGRIP1L is also known as COACH3, CORS3, FTM, JBTS7, MKS5, NPHP8, PPP1R134.

Associated Diseases

• Joubert syndrome with renal defect
• Joubert syndrome with hepatic defect
• Joubert syndrome 7
• Meckel syndrome, type 5
• COACH syndrome 3
• Meckel syndrome